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Audrey Bernstein

  • ASSISTANT PROFESSOR Ophthalmology
  • ASSISTANT PROFESSOR Pharmacology and Systems Therapeutics
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Education

  • B.S., Lehigh University
    Biochemistry

  • Ph.D., University of Kentucky Medical Center
    Biochemistry

  • Mount Sinai School of Medicine

Biography

    Dr. Bernstein is an Assistant Professor at Mount Sinai School of Medicine in the Departments of Ophthalmology and Pharmacology and Systems Therapeutics. She is a full-time researcher working on promoting regenerative healing and preventing fibrotic healing after wounding in the cornea and other tissues. 

Awards

  • 2009 -
    Special Scholars Award
    Research to Prevent Blindness

Research

Wound Healing and Fibrosis


Our lab is studying the mechanisms that regulate wound healing. Because corneal transparency is critical for clear, unobstructed vision, the cornea is an important model to investigate how to promote wound healing without fibrotic scarring. When the cornea is wounded by surgery or injury, its ability to refract light onto the retina (producing a properly focused image) is comprised if scarring occurs.  Our goal is to understand the mechanisms that promote wound healing without scarring and to apply these findings not only to the cornea but also to other fibrotic conditions in the eye and in other tissues (e.g., liver fibrosis).

 

Corneal wound healing begins when cells (fibroblasts) migrate into the wound site producing repair matrix. TGFb induces these fibroblasts to differentiate into contractile cells (myofibroblasts) that adhere to the surrounding matrix and pull the matrix fibers together, closing the wound. However, the persistence of myofibroblasts results in the overproduction of extracellular matrix, excessive contraction, and an autocrine loop of TGFb activity that leads to scarring. Our earlier research identified a role for proteases in modulating myofibroblast differentiation and persistence (see references below).

 

Recently, we discovered a previously unrecognized connection between de-ubiquitinases (DUBs) and fibrotic healing. DUBs remove ubiquitin from proteins, thereby saving them from degradation and stabilizing/increasing protein levels. We have identified specific DUBs that control myofibroblast adhesion, TGFb signaling, and extracellular fibrotic matrix accumulation. Furthermore, we have recently found that genetic silencing of these DUBs promotes regenerative healing, and prevents fibrotic marker development. Future studies will evaluate if these DUBs are novel targets for anti-fibrotic therapy. 

Research Topics

  • Cell adhesion and extracellular matrix
  • Cell migration
  • Cell differentiation
  • Proteases

Publications

Wang L, Pedroja B, Meyers E, Garcia A, Twining S, Bernstein A. Degradation of internalized αvβ5 integrin is controlled by uPAR bound uPA: Effect on β1 integrin activity and α-SMA stress fiber assembly. PLoS ONE 2012; 7(3).

Wang L, Ko CY, Meyers EE, Pedroja BS, Pelaez N, Bernstein AM. Concentration-dependent effects of transforming growth factor β1 on corneal wound healing. Molecular vision 2011; 17: 2835-2846.

Pedroja BS, Kang LE, Imas AO, Carmeliet P, Bernstein AM. Plasminogen Activator Inhibitor-1 Regulates Integrin αvβ3 Expression and Autocrine TGFβ Signaling. Journal of Biological Chemistry 2009; 284(31): 20708-20717.

Bernstein A, Twining SS, Warejcka DJ, Tall DJ, Masur SK. Urokinase receptor cleavage: a crucial step in fibroblast to myofibroblast differentiation. Molecular Biology of the Cell 2007 Sep; 18(7): 2716-2727.

Greenberg RS, Bernstein AM, Benezra M, Gelman IH, Taliana L, Masur SK. FAK-dependent regulation of myofibroblast differentiation. FASEB 2006; 20 (7): 1006-8.

Warejcka DJ, Vaughan KA, Bernstein AM, Twining SS. Differential conversion of Plasminogen to Angiostatin by Human Corneal Cell Populations. Molecular Vision 2005; 11: 859-868.

Taliana L, Benezra M, Greenberg RS, Masur SK, Bernstein AM. ZO-1: Lamellipodial Localization in a Corneal Fibroblast Wound Model. Invest Ophthalmol Vis Sci 2005; 46: 96-103.

Bernstein AM, Greenberg RS, Taliana LD, Masur SK. Urokinase Anchors uPAR to the Actin Cytoskeleton. Investigative Ophthalmology and Visual Science 2004; 45(9): 2967-2977.

Turner HC, Alvarez LJ, Candia OA, Bernstein AM. Characterization of Serotonergic Receptors in Rabbit, Porcine and Human Conjunctivae. Current Eye Research 2003; 27(4): 205-215.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Bernstein did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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